Fourier Magnetic Imaging with Nanoscale Resolution and Compressed Sensing Speed-up using Electronic Spins in Diamond

Optically-detected magnetic resonance using Nitrogen Vacancy (NV) color centres in diamond is a leading modality for nanoscale magnetic field imaging, as it provides single electron spin sensitivity, three-dimensional resolution better than 1 nm, and applicability to a wide range of physical and biological samples under ambient conditions. To date, however, NV-diamond magnetic imaging has been performed using real space techniques, which are either limited by optical diffraction to 250 nm resolution or require slow, point-by-point scanning for nanoscale resolution, e.g., using an atomic force microscope, magnetic tip, or super-resolution optical imaging. Here we introduce an alternative technique of Fourier magnetic imaging using NV-diamond. In analogy with conventional magnetic resonance imaging (MRI), we employ pulsed magnetic field gradients to phase-encode spatial information on NV electronic spins in wavenumber or k-space followed by a fast Fourier transform to yield real-space images with nanoscale resolution, wide field-of-view (FOV), and compressed sensing speed-up.Comment: 31 pages, 10 figure

Categorical dilemmas: challenges for HIV prevention among men who have sex with men and transgender women in Vietnam

In Vietnam, HIV continues disproportionately to affect men who have sex with men and transgender women, and the increase in HIV prevalence in these populations may be related to a lack of tailoring of current prevention approaches, which often fail to address social diversity within these populations. To effectively respond to HIV in Vietnam, it is imperative to identify sub-populations within the broad category of ‘men who have sex with men’ (MSM), a term which in Vietnam as in many other sites frequently subsumes transgender women. In this paper, we document the different categories used to describe people who engage in same-sex sexual practices and/or non-normative gender performances drawing on data collected via in-depth interviews and focus groups with a total of 79 participants in Hanoi. We identified over 40 different categories used to describe men who have sex with men and/or transgender women. These categories could be described as behaviourally-based, identity-based, or emic, and each carried different meanings, uses (based on age and geography) and levels of stigma. The categories shine light on the complexity of identities among men who have sex with men and transgender women and have utility for future research and programming to more comprehensively address HIV in Vietnam

Identifying factors for job motivation of rural health workers in North Viet Nam

BACKGROUND: In Viet Nam, most of the public health staff (84%) currently works in rural areas, where 80% of the people live. To provide good quality health care services, it is important to develop strategies influencing staff motivation for better performance. METHOD: An exploratory qualitative research was carried out among health workers in two provinces in North Viet Nam so as to identify entry points for developing strategies that improve staff performance in rural areas. The study aimed to determine the major motivating factors and it is the first in Viet Nam that looks at health workers' job perception and motivation. Apart from health workers, managers at national and at provincial level were interviewed as well as some community representatives. RESULTS: The study showed that motivation is influenced by both financial and non-financial incentives. The main motivating factors for health workers were appreciation by managers, colleagues and the community, a stable job and income and training. The main discouraging factors were related to low salaries and difficult working conditions. CONCLUSION: Activities associated with appreciation such as performance management are currently not optimally implemented, as health workers perceive supervision as control, selection for training as unclear and unequal, and performance appraisal as not useful. The kind of non-financial incentives identified should be taken into consideration when developing HRM strategies. Areas for further studies are identified

Physicians Infrequently Adhere to Hepatitis Vaccination Guidelines for Chronic Liver Disease

Background and Goals:Hepatitis A (HAV) and hepatitis B (HBV) vaccination in patients with chronic liver disease is an accepted standard of care. We determined HAV and HBV vaccination rates in a tertiary care referral hepatology clinic and the impact of electronic health record (EHR)-based reminders on adherence to vaccination guidelines.Methods:We reviewed the records of 705 patients with chronic liver disease referred to our liver clinic in 2008 with at least two follow-up visits during the subsequent year. Demographics, referral source, etiology, and hepatitis serology were recorded. We determined whether eligible patients were offered vaccination and whether patients received vaccination. Barriers to vaccination were determined by a follow-up telephone interview.Results:HAV and HBV serologic testing prior to referral and at the liver clinic were performed in 14.5% and 17.7%; and 76.7% and 74% patients, respectively. Hepatologists recommended vaccination for HAV in 63% and for HBV in 59.7% of eligible patients. Patient demographics or disease etiology did not influence recommendation rates. Significant variability was observed in vaccination recommendation amongst individual providers (30-98.6%), which did not correlate with the number of patients seen by each physician. Vaccination recommendation rates were not different for Medicare patients with hepatitis C infection for whom a vaccination reminder was automatically generated by the EHR. Most patients who failed to get vaccination after recommendation offered no specific reason for noncompliance; insurance was a barrier in a minority.Conclusions:Hepatitis vaccination rates were suboptimal even in an academic, sub-speciality setting, with wide-variability in provider adherence to vaccination guidelines. © 2013 Thudi et al

A gene signature for post-infectious chronic fatigue syndrome

Background: At present, there are no clinically reliable disease markers for chronic fatigue syndrome. DNA chip microarray technology provides a method for examining the differential expression of mRNA from a large number of genes. Our hypothesis was that a gene expression signature, generated by microarray assays, could help identify genes which are dysregulated in patients with post-infectious CFS and so help identify biomarkers for the condition. Methods: Human genome-wide Affymetrix GeneChip arrays (39,000 transcripts derived from 33,000 gene sequences) were used to compare the levels of gene expression in the peripheral blood mononuclear cells of male patients with post-infectious chronic fatigue (n = 8) and male healthy control subjects (n = 7). Results: Patients and healthy subjects differed significantly in the level of expression of 366 genes. Analysis of the differentially expressed genes indicated functional implications in immune modulation, oxidative stress and apoptosis. Prototype biomarkers were identified on the basis of differential levels of gene expression and possible biological significance Conclusion: Differential expression of key genes identified in this study offer an insight into the possible mechanism of chronic fatigue following infection. The representative biomarkers identified in this research appear promising as potential biomarkers for diagnosis and treatment

Proteomic and Functional Studies Reveal Detyrosinated Tubulin as Treatment Target in Sarcomere Mutation-Induced Hypertrophic Cardiomyopathy

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease. While ≈50% of patients with HCM carry a sarcomere gene mutation (sarcomere mutation-positive, HCMSMP), the genetic background is unknown in the other half of the patients (sarcomere mutation-negative, HCMSMN). Genotype-specific differences have been reported in cardiac function. Moreover, HCMSMN patients have later disease onset and a better prognosis than HCMSMP patients. To define if genotype-specific derailments at the protein level may explain the heterogeneity in disease development, we performed a proteomic analysis in cardiac tissue from a clinically well-phenotyped HCM patient group. METHODS: A proteomics screen was performed in cardiac tissue from 39 HCMSMP patients, 11HCMSMN patients, and 8 nonfailing controls. Patients with HCM had obstructive cardiomyopathy with left ventricular outflow tract obstruction and diastolic dysfunction. A novel MYBPC32373insG mouse model was used to confirm functional relevance of our proteomic findings. RESULTS: In all HCM patient samples, we found lower levels of metabolic pathway proteins and higher levels of extracellular matrix proteins. Levels of total and detyrosinated α-tubulin were markedly higher in HCMSMP than in HCMSMN and controls. Higher tubulin detyrosination was also found in 2 unrelated MYBPC3 mouse models and its inhibition with parthenolide normalized contraction and relaxation time of isolated cardiomyocytes. CONCLUSIONS: Our findings indicate that microtubules and especially its detyrosination contribute to the pathomechanism of patients with HCMSMP. This is of clinical importance since it represents a potential treatment target to improve cardiac function in patients with HCMSMP, whereas a beneficial effect may be limited in patients with HCMSMN

Replication Protein A (RPA) Hampers the Processive Action of APOBEC3G Cytosine Deaminase on Single-Stranded DNA

deamination assays and expression of A3G in yeast, we show that replication protein A (RPA), the eukaryotic single-stranded DNA (ssDNA) binding protein, severely inhibits the deamination activity and processivity of A3G. on long ssDNA regions. This resembles the “hit and run” single base substitution events observed in yeast., we propose that RPA plays a role in the protection of the human genome cell from A3G and other deaminases when they are inadvertently diverged from their natural targets. We propose a model where RPA serves as one of the guardians of the genome that protects ssDNA from the destructive processive activity of deaminases by non-specific steric hindrance

Rapid decrease of malaria morbidity following the introduction of community-based monitoring in a rural area of central Vietnam

<p>Abstract</p> <p>Background</p> <p>Despite a successful control programme, malaria has not completely disappeared in Vietnam; it remains endemic in remote areas of central Vietnam, where standard control activities seem to be less effective. The evolution of malaria prevalence and incidence over two and half years in a rural area of central Vietnam, after the introduction of community-based monitoring of malaria cases, is presented.</p> <p>Methods</p> <p>After a complete census, six cross-sectional surveys and passive detection of malaria cases (by village and commune health workers using rapid diagnostic tests) were carried out between March 2004 and December 2006 in Ninh-Thuan province, in a population of about 10,000 individuals. The prevalence of malaria infection and the incidence of clinical cases were estimated.</p> <p>Results</p> <p>Malaria prevalence significantly decreased from 13.6% (281/2,068) in December 2004 to 4.0% (80/2,019) in December 2006. <it>Plasmodium falciparum </it>and <it>Plasmodium vivax </it>were the most common infections with few <it>Plasmodium malariae </it>mono-infections and some mixed infections. During the study period, malaria incidence decreased by more than 50%, from 25.7/1,000 population at risk in the second half of 2004 to 12.3/1,000 in the second half of 2006. The incidence showed seasonal variations, with a yearly peak between June and December, except in 2006 when the peak observed in the previous years did not occur.</p> <p>Conclusion</p> <p>Over a 2.5-year follow-up period, malaria prevalence and incidence decreased by more than 70% and 50%, respectively. Possibly, this could be attributed to the setting up of a passive case detection system based on village health workers, indicating that a major impact on the malaria burden can be obtained whenever prompt diagnosis and adequate treatment are available.</p

The Circadian Clock Protein Timeless Regulates Phagocytosis of Bacteria in Drosophila

Survival of bacterial infection is the result of complex host-pathogen interactions. An often-overlooked aspect of these interactions is the circadian state of the host. Previously, we demonstrated that Drosophila mutants lacking the circadian regulatory proteins Timeless (Tim) and Period (Per) are sensitive to infection by S. pneumoniae. Sensitivity to infection can be mediated either by changes in resistance (control of microbial load) or tolerance (endurance of the pathogenic effects of infection). Here we show that Tim regulates resistance against both S. pneumoniae and S. marcescens. We set out to characterize and identify the underlying mechanism of resistance that is circadian-regulated. Using S. pneumoniae, we found that resistance oscillates daily in adult wild-type flies and that these oscillations are absent in Tim mutants. Drosophila have at least three main resistance mechanisms to kill high levels of bacteria in their hemolymph: melanization, antimicrobial peptides, and phagocytosis. We found that melanization is not circadian-regulated. We further found that basal levels of AMP gene expression exhibit time-of-day oscillations but that these are Tim-independent; moreover, infection-induced AMP gene expression is not circadian-regulated. We then show that phagocytosis is circadian-regulated. Wild-type flies exhibit up-regulated phagocytic activity at night; Tim mutants have normal phagocytic activity during the day but lack this night-time peak. Tim appears to regulate an upstream event in phagocytosis, such as bacterial recognition or activation of phagocytic hemocytes. Interestingly, inhibition of phagocytosis in wild type flies results in survival kinetics similar to Tim mutants after infection with S. pneumoniae. Taken together, these results suggest that loss of circadian oscillation of a specific immune function (phagocytosis) can have significant effects on long-term survival of infection